Dichlorination and Bromination of a Threonyl-S-Carrier Protein by the Non-heme Fe II Halogenase SyrB2
Bibliographic record
Abstract
Biosynthetic tailoring of nonribosomal peptide and polyketide natural products can enhance their biological activities. Tailoring enzymes can introduce alkyl, acyl, or glycosyl groups onto natural product scaffolds and can oxidize or halogenate biosynthetic intermediates. Chlorinated and brominated molecules make up more than 95 % of the more than 4500 known halogenated metabolites. Chloro and bromo substituents are frequently found on aromatic and heteroaromatic rings, and many terpene scaffolds are also brominated and chlorinated by marine microorganisms. Halogenating enzymes discovered to date fall into two categories based on their utilization either of hydrogen peroxide (haloperoxidases) or molecular oxygen (halogenases) as required oxidants. Haloperoxidases can contain either heme iron or a vanadate cofactor, thought to generate enzyme-bound hapohalite equivalents as proximal OCl or OBr. The O2-utilizing halogenases are typically found embedded in biosynthetic gene clusters; this suggests a tailoring role in specific natural product assembly. This second class of enzymes uses either FADH2 or non-heme FeII to activate chloride or bromide oxidatively. The flavoproteins work on electron-rich aromatic and heteroaromatic substrates. The FeII halogenases represent a new branch of the O2 and α-ketoglutarate-decarboxylating superfamily and are powerful enough to halogenate unactivated carbon centers on aminoacyl groups tethered to nonribosomal peptide synthetase assembly lines. Thus, the 4-Cl-L-Thr residue in the phytotoxic lipodepsipeptide syringomycin E (1) is generated by the non-heme FeII halogenase SyrB2 (Scheme 1). Chlorination occurs on the threonyl skeleton only while it is linked via a thioester to a peptidyl carrier protein domain. Remarkably, the cyclopropane ring in the amino acid coronamic acid arises by a similar γ-chlorination of an L-allo-Ile-S-protein by the halogenase CmaB. The γ-chloride is then displaced intramolecularly by a thioester enolate by action of CmaC. Therefore, the CmaB-mediated chlorination is cryptic in cyclopropane formation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".